INNOVATIONS IN ART

PROF.NARENDRA MALHOTRA
M.D., F.I.C.O.G., F.I.C.M.C.H, F.R.C.O.G.,F.I.C.S.,F.A.M.S.,FIAP
• Prof. Dubrovnick International University
• PRESIDENT ISAR 2016-17
• PRESIDENT ISPAT 2017-19
• President FOGSI (2008-2009)
• Dean I.C.M.U. (2008)
• Senior V. P. of FOGSI (2003)
• Vice Dean Indian College of Medical Ultrasound (2006)
• Director Ian Donald School of Ultrasound
• National Tech. Advisor for FOGSI-G.O.I.—Mc Arthur Foundation EOC Course
• Practicing Obstetrician Gynecologist at Agra. Special Interest in High Risk Obs., Ultrasound, Laparoscopy and
Infertility, ART & Genetics
• Member and Fellow of many Indian and international organisations
• FOGSI Imaging Science Chairman (1996-2000)
• Awarded best paper and best poster at FOGSI : 5 times, Ethicon fellowship, AOFOG young gyn. award, Corion
award, Man of the year award, Best Citizens of India award
• Over 30 published and 100 presented papers
• Over 50 guest lectures given in India & Abroad
• Organised many workshops, training programmes, travel seminars and conferences
• Editor 8 books, many chapters, on editorial board of many journals
• Editor of series of STEP by STEP books
• Revising editor for Jeatcoate’s Textbook of Gynaecology (2007)
• Very active Sports man, Rotarian and Social worker
MALHOTRA NURSING & MATERNITY HOME PVT. LTD.
GLOBAL RAINBOW HEALTH CARE,AGRA84, M.G. Road, Agra-282 010
Phone : (O) 0562-2260275/2260276/2260277, (R) 0562-2260279, (M) 98370-33335; Fax : 0562-2265194
www.malhotrahospitals.com,www.rainbow

INNOVATIONS IN A.R.T
prof narendra malhotra
prof jaideep malhotra
dr keshav malhotra
www.rainbowhospitals.org

DISCLOSURES
I have no financial relationship with the manufacturers
of any products or the
providers of any services that are mentioned in this presentation.
I do not intend to discuss any unapproved use of any device
mentioned in the presentation

In 1978 the world witnessed the birth of
the first “test tube baby.” Since this time
there have been
explosive innovations and advances in
assisted reproductive technologies (ART).
Steptoe PC, Edwards RG. Birth after the reimplantation of a human
embryo. Lancet. 1978;2(8085):366

Current innovations are in
1.delivery of in vitro fertilization (IVF) Tt.
2.utilization of minimal stimulation
protocols
3.increased use of GNRH antagonists
cycles and (GnRH) agonist triggers are
being increasingly utilized
4.maximize patient safety

• innovations, such as those seen in the
embryology laboratory, continue to improve
pregnancy rates
• Concurrent with these innovations and
advancements in IVF have been the emergence
of related technologies, such as embryonic
genetic testing and oocyte preservation, which
potentially have broad applications to both
fertile and infertile couples
• Many of the innovations and advances in ART
have both increased success rates and offered a
broad range of options to couples undergoing
treatment
Zhao Y, Brezina P, Hsu CC, et al.: In vitro fertilization: four decades of reflections and promises.
Biochim Biophys Acta. 2011:1810(9):843-52. Outlines the evolution of IVF, including
technological and social challenges

Technological innovations being developed
and perfected currently hold the potential to
change the field of ART in still more dramatic
and exciting ways well into the future.
As these relevant applications of ART
become increasingly utilized, it is incumbent
upon society to ensure that these resources
are made available in a morally responsible
and equitable manner.
Brezina PR, Zhao Y: The Ethical, Legal, and Social Issues Impacted by Modern Assisted Reproductive Technologies. Obstet Gynecol Int 2012,
2012:686253. Evaluates the ethical, legal and social challenges of ART that are most relevant to present-day society.

Here are some of the cutting edge
innovations in the field of ART and
the implications of these
technologies in the future.

IVF
INNOVATIONS & ADVANCEMENTS
clinical
• PREVENTION OF OHSS
• DEVELOPMENT OF MINIMAL STIMULATION
• ANTAGONIST PROTOCOLS
• PROTOCOLS(SOFT STIMULATION)
RECOMBINANT DRUGS
PREVENTION OF MULTIPLE GESTATIONS
SET/VIRTIFICATION
ART that will significantly improve the cost and safety
associatedwith IVF in the coming years.
Kresowik JD, Stegmann BJ, Sparks AE, et al. Five- years of a mandatory single-embryo transfer (mSET) policy dramatically reduces
twinning rate without lowering pregnancy rates. Fertil Steril. 2011;96(6):1367-9. A mandatory single-embryo transfer policy can
reduce the rate of multiple gestations with no change in delivery rate.

OHSS FREE CLINICS
paul devroy’s concept
Modified stimulation protocols
Freeze all stratergy
Preventive steps in PCOS and hyperresponders
Mild stimulation
Natural cycle IVF

MINIMAL STIMULATION
PROTOCOLS FOR WHO ALL ??
IF HYPERRESPONDER: YES
IF NORMAL RESPONDER:YES
IF POOR RESPONDER: ALSO YES

AIMS OF STIMULATION
Terminology Aim Methodology
Natural Single
oocyte
No medication
Modified natural Single
oocyte
hCG only
Antagonist/
FSH addback
Mild stimulation 6-7 oocytes Softer protocols
Conventional More than 8
oocytes
Conventional
protocols
VALORACIÓN DE LA FUN
OVARICA CON 4D

Effect of dose
Higher dose does
not mean better
outcome

Dosage Of Gonadotropins
AGE
PCOS-FSH
Hyperresponders Normal responders
<30 yrs 50/75iu 50/75iu
30-35 yrs 50-75iu 100-150iu
>35 yrs 150 iu 150iu

CHANGING APPROACH(INNOVATION)
YESTERDAY
TODAY
TOMORROW
CONVENTIONAL
MILD/MINIMAL
INDIVIUALISED
More Oocytes
Supraphysiological E2
Agonist protocols
More embryos/OHSS
Multiple pregnancies
Cryopreservation
Less Oocytes
Optimal E2
Antagonist protocols
No OHSS
No multiple pregnancies
Lower cost
Optimal Oocytes/Embryos
No OHSS
No Multiple pregnancies
Lower cost
PATIENT FRIENDLY

Laboratory Innovations
• Probably the single most significant factor in
the dramatic improvement in IVF pregnancy
rates over the past 10-15 years has been the
technological modifications and innovations
in the embryology laboratory
• perfecting the embryo culture media has likely
been the most significant
• Optimal enviorment GASES(OXYGEN),PH
• Other techniques like assisted hatching

FANCY GADGETS IN QUALITY
MANAGEMENT IN THE LAB
How Useful are they ???

7. Plumbing
6. Light
1. Oocyte
2. Temperature
3. pH
4. Osmolality
5. Air quality

8. Timing
10. Security
11. Embryotoxicity
12. Culture Medium
13. Supplies – Consumables
14. Cleaning
9. Ovarian Hyperstimulation

OOCYTE
OOCYTE OPTIMAL REQUIREMENTS:
 Low aspiration pressure (<120mm
Hg) - Pressure;
Parthenogenesis
 Temperature of 370C
 pH of 7.3 to 7.35 (dependant on
culture medium)
 Osmolality 275 - 290 mOsm/kg
 Low O2 (5% O2; 6% CO2; 89% N2)
 Bols et al reported highest # oocytes
with 18g OPU needle
Optimal flow rates 20 – 25 mL/min =
24 to 30 seconds to aspirate 10 mL of water
The oocyte requires consistent conditions (temperature, pH, osmolality from collection
to transfer
The embryologist goal is to ENSURE THIS STABILITY. Lopata, A. et al Fertil. Steril. 1974; 25:1030-8
Bols, P.E.J. et al Theriogenolgy 1996; 45:1001-4

INNOVATIVE TEMP CONTROL GADGETS IN THE LAB

INNOVATIVE PH MONITORING GADGETS

OSMOLALITY
OSMOLALITY is the measure of solute
particles dissolved in a solution
as calculated by an osmometer expressed
as milliosmoles / kilogram (mOsm/kg)
OSMOLARITY is the measure expressed in
milliosmoles / litre (mOsm/L) and is less
accurate as calculated in terms of
solvent volume The difference depends
on how the concentration was derived.
Solute concentration can exert osmotic
pressure –
impacting on cell volume and stressing
development
Osmolality Shift Factors:
 Media volume - 10μl, 20μl, 40μl
 Temperature of preparation surface –
370C or 230C
 Air flow – on or off
 Time of preparation
 Media composition (initial osmol. &
osmolytes)

ENVIRONMENT
Time: Open System: Closed System:
Temperature
:
pH: Temperature
:
pH:
0 mins. 36.00C ± 0.1 7.31 ± 0.01 36.50C ± 0.1 7.3 ± 0.01
3 mins. 35.20C ± 0.3 7.38 ± 0.02 36.60C ± 0.1 7.33 ± 0.04
20 mins. 35.20C ± 0.3 7.55 ± 0.02
(Did not begin to drop for 15 mins &
still elevated at 90 mins.)
36.60C ± 0.1 7.33 ± 0.04
Work Station Temperature & pH Fluctuations:
 Hyslop L. et al compared environmental conditions between a unique
chain of enclosed workstations with incubators (temperature & CO2
controlled) set at air temp. 35.00C & hotplate at 37.20C & open
stereomicroscope in a conventional Class II cabinet with heated surface set
at 37.40C
 500 μl of pre-warmed culture medium with an overlay of 700 μl of mineral
oil in an organ culture dish (Initial temp. loss in transfer from incubator
to Class II cabinet)
Hyslop, L. et al PLoS ONE 7(2): e31010. doi:10.1371/journal.pone.0031010 (2012)

AIR QUALITY
 Richard Legro et al 2010 noted the effects of declining air quality on reproductive outcomes after IVF are
variable but increased nitrogen dioxide (NO2) is consistently associated with lower live birth rates.
 Fine particulate matter (PM2.5) in the IVF laboratory during embryo culture was associated with decreased
conception rates.
 USA EPA considers significant risk to humans and fertility following exposure to certain chemicals, VOCs &
particulate matter

AIR QUALITY MEASURING
DEVICES:INNOVATIONS
CODA (Activated Carbon) Filters in Incubators
help remove:
Styrene
Acetone
Benzene
Toluene
Octane
N-Decane
Freon
Aldehydes
Nonane
Methylcyclohexane
Butane
VOC levels >1 ppm - toxic to embryos
Levels around 0.5 ppm – miscarriages
Levels <0.2ppm – 0 best outcomes
UV lights remove microorganisms

SUPPLIES & CONSUMABLES
Innovative features for enhanced results:
 Facilitate gas exchange with vented lid
 Choose the correct size for your application; available in in 35mm, 60mm and
90mm sizes
 Certificates of conformity available for every lot
Rigorously tested, certified and validated for IVF:
 CE-marked, FDA cleared and MEA tested
 Produced under ISO 13485 with full lot traceability
 Sterile (SAL 10-6)
 Non-pyrogenic (LAL test)
 USP Class VI test
 Release test results (MEA)
Determine what is required
&
if it meets your requirements
Gamma Irradiation sterilization –
No toxic residue

35
STEAM:
Vapour steam cleaners or steam vapour systems are cleaning appliances or devices that use steam to quickly
dry, clean, and sanitize inanimate surfaces. Often the process is effective enough to disinfect or even sterilize
the surfaces. The steam is produced in a boiler that heats tap water to high temperatures (240-310F/115-
155C) to produce low-pressure (several atmospheres), low moisture (4 to 6% water) water vapour (steam).
The steam's ability to clean is based primarily on its heat. The steam is applied to cleanable surfaces via a
variety of insulated tools and accessories, thereby safely providing the energy needed to break soil bonds and
release contaminants into water suspension, after which they can be removed by wiping or vacuuming.
Active Ingredients: Water
INNOVATIVE CLEANING TOOLS

SECURITY & SAFETY
36
ART LABORATORY RISKS:
What could go wrong & have a significant effect on outcomes?
RISK: MITIGATION STRATEGY:
Loss of power Generator / UPS
CO2 / Special Gas Mix failure Automatic Gas Changeover manifold; Regulators
LN2 Storage Tank emptying LN2 Level alarms; Regular measuring / top up of tanks;
Replacement at end of life span;
Safety training
Staff member injured Low O2 level & high CO2 alarms; PPE; fire alarms /
extinguishers
Break in to laboratory Security monitoring; Security response;
Locks on LN2 tanks
Equipment failure Back to base alarm system; spare equipment; service /
maintenance contracts;
arrangements with competitors
IT virus / hacking – loss of data Regular backups (stored offsite);
Antivirus software

BETTER INNOVATIVE
STORAGE OPTIONS
INCREASED CAPACITY
AUTOMATIC REFILLING
INTEGRATED ALARM SYSTEM
DEFOGGING MECHANISM

INNOVATIVE WITNESSING SYSTEMS
BAR CODING ON ALL SUPPLIES

DATA MANAGEMENT
DATA MANAGEMENT
Paperless
Easy access
Improved management
Cloud based Record management
Easy scheduling
Improved Accountability
ISAR FREE DATA MANAGEMENT
SOFT WARE

DATA MANAGEMENT
DATA MANAGEMENT

Future innovations in the IVF lab
Giles Palmer
Mitera IVF, Athens

Future developments in the IVF lab
IVF WITHOUT LAB

Future developments in the IVF labAutomation of ICSI
• Since 1992 : male infertility
• Experience operator, highly skilled
• Auto injection – transgenics
• Use of MEMS and micro-robotics,
Nano-newton force sensors, Servo
optical control
• RICSI : 7200 per second with an
accuracy of 0.240, Immobilization of
sperm in 6-7 seconds (CASA
adapted)
• Survival rate 90% (Sun 2011)
• Human trials on going

Further developments of in vitro culture
• 40 years on…Biggers, Brinster
• Basic physiological principles of Leese, Quinn and Gardner
• In vitro culture sub-optimum (Schieve 2002, Richter 2008)
• Call for “new generation media” with bio active factors

GM-CSF
Future developments
in the IVF lab
• GM-CSF in IVF medium improves
success rates in Recurrent
Implantation Failure patients
(Spandorfer et al., Am J ReprodImmunol 2008)
• GM-CSF is reduced in recurrent
miscarriage patients
(Perricone et al Am J Reprod Immunol 2003)
• Follicular fluid GM-CSF is
reduced in women experiencing
unexplained infertility
(Calogero et al., Cytokine 1998)
Positive effect on cell number,
implantation, blastocyst formation,
regulates apoptosis
Robertson 2011, Sjoblom 1999

“Lab on a chip”
Sperm sorting
Imaging
Co-culture
Oxygen consumption
Biomarker analysis

INNOVATIONS :Reality or Gimmicks

INNOVATION IN
Assisted Reproductive Technology
Innovations For Treating Infertility:
One Boosts ICSI And IVF Success
Rates
THE SPERM

V I T A L I T Y
CHOOSING THE RIGHT SPERM
ICSI
PICSI
IMSI
LASERS to IMMOBILISE

Sperm dna fragmantation
Is your phone cooking your sperm?
They’ve been blamed for causing everything
from Alzheimer’s disease to cancer, and now
infertility. Here’s a look back at popular mobile
phone health scares gone by …

Chromosomal Aneuploidy
FLUORESCENCE IN SITU
HYBRIDIZATION
PROVIDES A METHOD
TO TEST FOR SPERM
CHROMOSOMAL
ANEUPLOIDY.
THE SPERMATOZOA OF
INFERTILE MEN EXHIBIT
A 10-FOLD HIGHER
INCIDENCE OF
CHROMOSOME
ANEUPLOIDIES
(TESTING FOR
CHROMOSOMES X, Y,
13, 18, 21—THOSE
COMPATIBLE WITH A
LIVE BIRTH)

SEEING SPERM
• Taking this into account, the Tel Aviv
University scientists developed a
technology allowing scientists to perform
clinical sperm analysis without the use of
staining.
• new device, a black box that is attached
to a microscope and joined to software,
harnesses phase imaging methods to
assess the quality of sperm
• new tool is small, cost-effective, and
easier to use than conventional
interferometric imaging methods and so,
he believes, it will lead to greater success
when using ART treatments

Spermobikes:SPERMBOTS
“
Low motility” problems, when healthy sperm just can’t swim, are one of the main causes of
infertility. To give slow swimming sperm a helping hand, the German science team developed
a unique solution: the Spermbot
Based on previous work with micromotors, the researchers constructed mini-metal motorized
helices just large enough to fit around the tail of a sperm. Using a rotating magnetic field as the
joy stick, the researchers can direct the micromotor helices to slip around a sperm cell, to drive
the sperm to an egg, and then to release the sperm for potential fertilization. Essentially, the
spermbot serves as a power motor.

Laboratory Advancements and
Innovation
In Vitro Maturation (IVM)
• The ability to mature oocytes in a laboratory environment, in vitro
maturation (IVM), is another innovative technology that is being
currently perfected by many centers.
• IVM, as currently described, is the practice of retrieving immature
human oocytes which then complete the transition from prophase
I to metaphase II, including extrusion of the 1st polar body, in
vitro
• The benefit of IVM in today’s current clinical environment is
unclear and will need to be further explored
Picton HM, Harris SE, Muruvi W, Chambers EL.
The in vitro growth and maturation of follicles.
Reproduction. 2008;136: 703–15

Laboratory Advancements and
innovation: Cryopreservation
• Perhaps the most significant innovation in
embryologic laboratory technology in recent
years has been in the field of cryopreservation
• Applying cryopreservation to IVF embryos was
achieved relatively early in 1983 when the first
pregnancy resulting from a cryopreserved
embryo was reported
• The process used to cryopreserve embryos has
evolved since this time and many innovations
have been done in this field.
Shufaro Y, Schenker JG. Cryopreservation of human genetic material. Ann N YAcad Sci.
2010;1205:220–4.

• oocyte cryopreservation protocols using
vitrification, including the introduction of the
equipment innovations such as the cryotop, have
been continuously optimized
• These techniques resulted in oocyte survival rates
following cryopreservation approaching 90 % by
2005
• . Currently, multiple clinics report pregnancy rates in
cycles utilizing oocyte cryopreservation that
approach those seen in fresh IVF cycles
• However, the practice of oocyte cryopreservation is
still considered an experimental technology
according to the American Society for Reproductive
Medicine (ASRM)

• The demonstration that oocyte
cryopreservation is now a viable
alternative to embryo
cryopreservation has broad
implications. The application of
this technology that could
impact the largest proportion
of society is for women who
wish to preserve their fertility.
Women who pursue professional
careers are increasingly delaying
childbearing compared to historical
normsBroekmans FJ, Soules MR, Fauser BC. Ovarian aging:
mechanisms and clinical consequences. Endocr Rev.
2009;30(5):465–93.

Fertility presevation in cancers
• Oocyte cryopreservation has additional
applications that are currently being utilized
• Oocyte cryopreservation is increasingly being
offered as a method of fertility preservation for
oncology patients prior to receiving chemo or
radiation therapy
• Cryopreservation of unstimulated ovarian
cortical tissue for the purpose of fertility
preservation for oncology patients has also been
performed, although with limited success

• As donor oocyte cycles currently
comprise approximately 10 % of
all IVF cycles, egg banks, from a
systems point of view, represent
a significant innovative advance
in quality and efficiency

Innovative EGG BANKS
Another application for oocyte cryopreservation is the recent
creation of donor oocyte
“egg banks”
for use in donor oocyte cycles. Traditionally, donor oocyte
cycles demanded that the cycles of the donor and recipient be
coordinated. Egg banks eliminate the need for this time
consuming and costly process while offering increased choices
to couples undergoing a donor oocyte IVF cycle
INDIA HAS EGG BANKS : YES, MOST OF
US
NOW ARE DOING EGG BANKING IN
INDIA,
WHENEVER WE GET DONORS
…STIMULATE AND FREEZE

Innovations inTechnologies Evaluating
Embryos
• Traditionally, embryo morphology has been the most
utilized method of determining embryo quality.
• There are numerous grading systems that have been
developed to grade embryo morphology .
• However, embryo morphology alone has been shown
to be a suboptimal indicator of determining which
embryos have normal chromosomal status (euploidy)
or optimal implantation potential .
• For this reason, a variety of different modalities have
been developed to evaluate embryo quality both
directly and indirectly.

Technologies Evaluating Embryos
Preimplantation Genetic Diagnosis
(PGD)& (PGS)
• Preimplantation genetic diagnosis (PGD) and
preimplantation genetic screening (PGS)
involve obtaining one or more cells from the
developing embryo and evaluating the genetic
composition of this cell(s) for either a specific
genetic defect known to exist in the parents
(PGD) or to screen for the presence of embryo
aneuploidy (PGS)

PRE-IMPLANTATION
GENETIC DIAGNOSIS
AND SCREENING
ANOTHER GAME
CHANGING INNOVATION

Reproductive choices for couples at
genetic risk
• No testing
• No children
• Adoption
• Donor egg/sperm or embryo
• Prenatal testing: CVS or
amniocentesis
• Preimplantation Genetic Diagnosis
(PGD)

Which IVF unit should offer PGD?
• Before offering PGD, the IVF clinic needs to
ensure that it has a good IVF pregnancy rate
• Pregnancy rate following PGD is lower than
general IVF pregnancy rate –
– Potential impact of biopsy procedure - Less cycles
proceed to transfer - Fewer “normal” embryos
available for transfer (may not be possible to select
an embryo with good morphology for transfer)
• To offer PGD to patients, we need to
demonstrate that the benefit of PGD
outweighs the impact of the biopsy procedure

Embryo Biopsy
Polar Body Biopsy (Day 0-1)
Advantages:
• Less invasive? - Polar bodies have no role in the
development of the embryo
• Biopsy has no detrimental effect on oocyte
fertilisation rates or further embryo development
• Blastomere or blastocyst biopsy available as
confirmation or backup
Disadvantages:
• Restricted to the diagnosis of maternally derived
abnormalities - Paternal abnormalities will go
undetected
• First polar body is often fragmented - Potential for
misdiagnosis based on an inability to recover all DNA
fragments

Embryo Biopsy
Blastomere Biopsy (Day 3)
Advantages:
• Removal of 1-2 cells does not appear to affect
development
• Diagnosis of maternal and paternal abnormalities
• Most frequently performed method of biopsy
Disadvantages:
• Only 1-2 cells available for analysis
• Chromosomal mosaicism in the embryo - Does the
biopsied cell accurately reflect the constitution of the
embryo?
• Embryos typically start to undergo compaction on Day
3
• Removal of a single blastomere can be difficult –
Incubate in Ca/Mg-free media before biopsy
• Rapid diagnosis required for Day 4 or Day 5 transfer

Embryo Biopsy
Blastocyst Biopsy (Day 5/ Day 6)
Blastocyst biopsy has been associated
with:
• Higher implantation rate than Day 3
(regardless of maternal age)
• Lower aneuploidy rate than Day 3
• Reduced mosaicism compared with
Day 3
• More cells available for analysis

• PGS evaluating 23 chromosomes and day 5
biopsy has resulted in excellent pregnancy
rates in specific patient populations such as
couples suffering from recurrent pregnancy
loss (RPL) .
• The recent technological advances in
preimplantation genetic testing suggest that
there will be a wider implementation of
PGD/PGS in the future
Benner AT, Brezina PR, Du L, et al. 23-chromosome single nucleotide polymorphism (SNP)
microarray preimplantation genetic screening (PGS) on blastocysts, versus day-3 embryos,
results in significantly higher clinical pregnancy rates. Fertil Steril. 2011;96 (3):S221.

• Innovations in genetic medicine are
increasingly linking medical conditions to
specific genetic markers .
• The expansion of genetic medicine in the
future will certainly broaden the applications
of medically indicated PGD.
Kuliev A, Verlinsky Y. Current features of
preimplantation genetic diagnosis. Reprod
Biomed Online. 2002;5(3):294–9.

Technologies Evaluating Embryos:
Preimplantation Genetic Screening
(PGS)
• Chromosomal aneuploidy is believed to be the
single greatest causal factor in pregnancy failure
• PGS is the practice of evaluating cells from a
developing embryo for the purposes of
identifying aneuploidy
• PGS was introduced as a technology that could
greatly improve pregnancy efficiency in IVF
patients at risk for miscarriage such as couples
suffering from recurrent pregnancy loss or
patients with advanced maternal age.
. Harton GL, De Rycke M, Fiorentino F, et al. European Society for Human Reproduction and Embryology
(ESHRE) PGD Consortium. ESHRE PGD consortium best practice guidelines for amplification-based PGD. Hum
Reprod. 2011;26(1):33–40.

Day 14 embryo culture
Transfering day 13-14 will increase success rates …permission applied

Assisted Hatching the embryos
before transfer…LASERS

OMICS
• OMICS informally refers to a field of study in
biology
• The related suffix -ome is used to address the
objects of study of such fields, such as the
genome, proteome or metabolome
respectively

GENOMICS is the BUZZ word now
• Genomics: Study of the genomes of organisms
• Cognitive genomics examines the changes in cognitive processes associated with
genetic profiles
• Comparative genomics: Study of the relationship of genome structure and
function across different biological species or strains
• Functional genomics: Describes gene and protein functions and interactions (often
uses transcriptomics)
• Metagenomics: Study of metagenomes, i.e., genetic material recovered directly
from environmental samples
• Personal genomics: Branch of genomics concerned with the sequencing and
analysis of the Epigenomics: Study of the complete set of epigenetic modifications
on the genetic material of a cell, known as the epigenome. ChIP-Chip and ChIP-Seq
technologies used.

Technologies Evaluating Embryos:
Secretomics and Metabolomics
• Secretomics and metabolomics offer another
strategy of determining which embryos are
optimal to consider for uterine transfer .
• These technologies attempt to determine
information about embryos from byproducts that
can be measured in the media culture fluid
surrounding the developing embryo .
• One important advantage of these approaches is
that they provide a noninvasive manner to
evaluate embryos versus invasive techniques that
require embryo biopsy.
.Katz-Jaffe M, Gardner DK. Can proteomics help to shape the future of human assisted
conception? Reprod Biomed Online. 2008;17:497–501.

Lipidomics
• Lipidome is the entire complement of cellular
lipids, including the modifications made to a
particular set of lipids produced by an
organism or system
• Lipidomics: Large-scale study of pathways and
networks of lipids. Mass spectrometry
techniques are used.

Proteomics• Proteome is the entire complement ofproteins,
including the modifications made to a particular set of
proteins, produced by an organism or system
• Proteomics: Large-scale study of proteins, particularly
their structures and functions. Mass spectrometry
techniques are used.
• Immunoproteomics: study of large sets of proteins
(proteomics) involved in the immune response
• Nutriproteomics: Identifying the molecular targets of
nutritive and non-nutritive components of the diet.
Uses proteomics mass spectrometry data for protein
expression studies
• Proteogenomics: An emerging field of biological
research at the intersection of proteomics and
genomics. Proteomics data used for gene annotations
• Structural genomics: Study of 3-dimensional structure
of every protein encoded by a given genome using a
combination of experimental and modeling
approaches.
Proteomics to Develop more suitable
Cryopreservation Conditions
The ability to quantitate developmentally
important molecules may potentially form the
basis for the development of non-invasive
viability assays

Metabolomics
• Scientific study of chemical processes involving
metabolites. It is a "systematic study of the
unique chemical fingerprints that specific cellular
processes leave behind", the study of their small-
molecule metabolite profiles
• Metabonomics: The quantitative measurement of
the dynamic multiparametric metabolic response
of living systems to pathophysiological stimuli or
genetic modification

• The “OMICS” have been have been of
enormous value in the optimization of
embryo culture and cryopreservation .
• More recently their ability to assist with
the
identification of viable euploid
embryos has
been the focus of great attention.

METABOLOMICS
• Significance of metabolism to
embryo development and viability
• Energy is fundamental to the
survival and development of any
cell.
The metabolism of the
preimplantation embryo changes
during development and
• differentiation.
• Loss of metabolic regulation is
associated with poor development
and a loss of viability.

NON INVASIVE TECHNIQUES
• Spectroscopy
• Fluorescence / Microfluorescence
• Self-referencing electrode
• HPLC
• LC-MS QQQ
• Raman
• Near Infra-Red Spectroscopy
• NMR
• Laboratory on a Chip /
Microfluidics

Technologies Evaluating Embryos
Time Lapse Imaging
• Another recent development
in noninvasive evaluation of
developing embryos is the
use of time lapse imaging and
videography.
• This emerging field offers yet
another technology that, as it
is perfected, may be a
powerful tool to select
embryos best suited for
uterine transfer in IVF cycles.

MITOCHONDRIA AND THE EGG !!
What role does it play???

MATURING OOCYTE
• Close metabolic
synchronization between
oocyte and follicle
• Gradual increase in organelle
number GV-MII
• Changes in organelle
morphology with stage of
maturation in adult cycling
ovary and with other
organelles (ER, microtubules)

Diagrams of TEM images - Motta et al, 2000
*Dalton CM, Carroll J. J Cell Sci. 2013 pt13:2955-64.

mitochondrial distribution affects the cytoplasmic microtubule structure and thus
may lead to abnormal ATP distribution which could hinder the development of the
oocyte
(Hu et al., 2012).

Mitochondrial homogeneous
distribution.
Sub membrane HALO
Better Blastocyst Formation
rates!!
Decreased mitochondrial levels
More likely to arrest !!

NEWER RESEARCH
• Nuclear genome transfer.(NGT).
• Polar Body Genome Transfer (PBT).

• Involves extraction of primordial Germ
Cells(PGC’s) from the parent ovary.
• Extraction of Mitochondria from PGC’s
• Injecting Concentrated mitochondria into
eggs
Robert Casper, M.D., F.R.C.S.C

Sounds SIMPLE RIGHT ?
• Lot of intricacies involved
– How to extract mitochondria ?
– How Much mitochondria to inject ?
– Long term Complications ?
– Will it work ?
– Selecting the right Candidates ?
– How successful is it?

• There is a large pool of probable patients
AGING Women
WHO WOULD USE THIS ??

WHO WOULD USE THIS ??
• Women who have inheritable mitochondrial
disease and who want to have children have
four other options to avoid passing on
mutated mtDNA:
– Adoption
– egg donation
– prenatal genetic diagnosis
– preimplantation genetic diagnosis.

3-person IVF
would result in
inheritable
genetic
modification.
WHOLE NEW FORM OF DESIGNER BABIES

Exclusive: World's first baby born with new
“3 parent” technique | New ...
• https://www.newscientist.com/.../21
07219-exclusive-worlds-first-baby-
b...
• Sep 27, 2016 - A five-month-old boy
is the first baby to be born using a
new technique that incorporates
DNA from three people, New
Scientist can reveal. ... The
controversial technique, which
allows parents with rare genetic
mutations to have healthy babies,
has only been legally approved in the

SO CAN THIS BE DONE IN EGGS ???

First Baby Born Using Innovative Stem
Cell In Vitro Fertilization Technique
• Zain Rajani was born by
taking an ovarian tissue
sample from his mother,
Natasha Rajani. Her tissue
sample was analyzed in
order to identify egg stem
cells. Once the egg stem cells
were identified, they were
removed from the tissue and
purified. The purification
process allowed for the
extraction of the
mitochondria, organelles
that provide energy for cell,
in the egg stem cells. The
introduction of
mitochondria provided a
more reliable source of
energy for the egg cells and
helped produce a healthy
embryo for Natasha,
resulting in Baby Zain.
First Baby Born with Help From Stem Cell IVF |
Fit Pregnancy and Baby
www.fitpregnancy.com/pregnancy/.../first-
baby-born-help-stem-cell-ivf
At nearly one month old, Canadian baby Zain
Rajani is the first baby born in the world with a
new in vitro fertilization (IVF) treatment that
uses stem cells

GAME CHANGING INNOVATION IN
ART
• Fascinating opportunity for Older women
trying to concieve.
• Considerable Gaps between existing
knowledge and its implementation.
• Ethical dilemma
• GAME CHANGING TECHNOLOGY !!!

Ovarian transposition
(The ovarian dose is reduced by transposition to 5–10%)
A) Medial transposition
Behind the uterus.
B) Lateral transposition
up to the pelvic sidewall at least 3cm
from the upper border of the radiation
field.
techniques * by laparotomy during surgery.
* by laparoscopy
- higher doses of radiation are more likely associated
with vascular damage of transposed ovaries.

Reproductive function of transposed ovaries.
• 89% spontaneous pregnancy with 75%
occurring without repositioning.
• 11% conceived with IVF.

Ovarian tissue transplant
• Imagine ovarian tissue transplanted on
your fore arm
• Oocyte retrieval from just under skin

first mom-daughter uterus transplant
and this mother has delivered also
• STOCKHOLM — Two Swedish women are
carrying the wombs of their mothers after
what doctors called the world's first mother-
to-daughter uterus transplants.

Playing God
the Arrogant Misuse of Science

Baby lust seems to obliterate any sane calculus
of the real life dangers involved both to the
would be parents
And
the Clinicians playing God here….

DESIGNER BABIES
• BLUE EYES
• GOLDEN HAIR
• FAIR SKIN
• TALL
• INTELLIGENT
• WELL BUILT
• LIKES OF PRIYANKA AND
HRITHIKS
POSSIBLE FOR A PRICE

DESIGNING BABIES TO SAVE SICK
SISTERS/BROTHERS
• Another application for PGD is Human Leukocyte Antigen
(HLA) typing .
• This technology is generally employed by parents who have
a child affected by a particular disorder that could benefit
from some sort of human tissue transplant.
• For example, a child with leukemia who requires a bone
marrow transplant.
• In these cases, PGD has been employed as a modality to
ensure that the next child that the couple conceives will be
HLA compatible with their existing child with the given
illness.
• This practice is relatively uncommon but has generated
considerable debate regarding the ethics of HLA typing PGD

where are we headed from
here………..

ALARMING?
SCIENTIFIC ADVANCES
IN HUMAN
REPRODUCTION
TOMORROW IS HERE

• If we could translocate short arm
of Chromosome-6 and locate it on
a animal’s embryo we could
produce animals for spare parts
(Liver, Heart, kidneys)
• (Monkeys, Apes, Pigs, Baboons)
`
Chromosome—6
SHORT ARM HAS
HISTOCOMPABILITY GENES

Stem cells to produce gametes -2007
• Sperms and occytes from same
person(THEORETICALLY YOU WILL BE THE
GENETIC FATHER AND MOTHER OF YOUR
CHILD)
• Sperm from one palm
• Oocyte from the palm of other hand
• A shake hand will produce a baby

Stem Cell Researchers’ Discovery
Will Allow Gay Couples To Create
Their Own Eggs
My two dads may soon be a genetic reality. Scientists
have discovered how to create a baby with the DNA of
two fathers without the need for a donated egg.

ARTIFICAL GAMETES
• SPERMS
• OOCYTES
NOW THESE CAN BE MADE FROM ADULT
CELLS AND AZOSPERMICS AND OVARIAN
FAILURE CASES WILL HAVE HOPE OF GENETIC
OFFSPRINGS

MONKEY’S MADE FROM
ARTIFICAL GAMETES

Japanese stem cell research inspires
US scientists to create a lab human
sperm
• A team of Japanese scientists at
Kyoto University has successfully
created fertile eggs through the use
of stem cells. Their experiment
resulted in mice having healthy
babies. Taking the research forward
is Dr Renee Pera, of Stanford
University in California, who hopes
to soon create human sperm using
stem cells.

Lab-Made Eggs Raise New Fertility Options
Early-Stage Cells Used to Produce Healthy Mice;
Could the Dead Become Parents?
• Japanese scientists have made viable mouse
eggs in a laboratory dish, an advance that may
offer a new route for treating infertility in
people.
• The experiment completes a long-sought quest
in reproductive biology: to make sperm and
eggs in a lab dish. A year ago, the same core
group of scientists at Kyoto University created
healthy mouse sperm in the lab.
• In the latest experiment, the dish-created eggs
were fertilized with natural mouse sperm to
create healthy, fertile mice. The research
appears in the journal Science

The technologies that are coming
of age now and are visible on the
horizon have the potential to
expand the utilization of ART to
broad portions of society with and
without an infertility diagnosis.

• The scope of recent advances and
innovations in the field of assisted
reproductive technologies is staggering
• ART has had a tremendous impact on
medicine since its introduction in 1978.
• Tremendous innovations have taken
place and are taking place every day

For infertile couples, these
innovations promise to further
improve the effectiveness,
convenience, and availability of
infertility treatment while
driving down costs with
economies of scale and other
efficiencies

INNOVATIONS IN ART

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